We have observed that changes in the fat composition of the diet fed to tumor bearing mice alter the lipid composition of L1210 murine leukemia cells growing in these mice. This proposal is designed to examine the effect of diet-induced alterations of the lipid composition of membranes on cell function. The phospholipids of the cell membranes would be of special interest since changes in them might result in variations in membrane properties and functions, including the transport of antineoplastic drugs. The hypothesis will be examined in two systems: 1) L1210 mouse leukemia cells from animals fed either a high saturated or polyunsaturated fat diet, and 2) leukocytes obtained from normal human volunteers fed either a high saturated or polyunsaturated fat diet. In the animal model, the median survival of animals carrying the L1210 leukemia and receivng concurrent anti-neoplastic drugs will be compared for those animals receiving either a high saturated or polyunsaturated fat diet. We will characterize the changes in membrane lipids which occur in the neoplastic cells from these animals and these changes will be analyzed in relation to changes in membrane physical properties such as fluidity. In addition, we will examine the function of enzymes located within or upon the membrane and the transport of drugs across the membrane. The function of leukocytes from normal human subjects on experimental diets will be examined (phagocytosis, chemotaxis, incorporation of fatty acid, transport of drugs as well as the membrane lipid changes which result from the diets.